Functional and cellular interactions between nitric oxide and prostacyclin

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 129; no. 4; pp. 349 - 359
• Main Authors: Marcelı́n-Jiménez, Gabriel, Escalante, Bruno
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2001
• Subjects: Animals; Arachidonic acid; Arachidonic Acid - pharmacology; Cell Culture Techniques; Coronary circulation; Coronary Vessels; Cyclic GMP-Dependent Protein Kinases - metabolism; Cyclooxygenase; Cyclooxygenase 1; Endothelial cells; Endothelium - cytology; Epoprostenol - biosynthesis; Guanylate cyclase; Heart - physiology; Isoenzymes - metabolism; Isolated perfused heart; Male; Membrane Proteins; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Nitric oxide; Nitric Oxide - pharmacology; Nitrovasodilators; Phosphorylation; Prostacyclin; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Wistar; Vasodilation; Isolated perfused heart; Cyclooxygenase; Nitric oxide; Nitrovasodilators; Prostacyclin; Coronary circulation; Arachidonic acid; Guanylate cyclase; Endothelial cells
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/S1532-0456(01)00210-1

Nitric oxide (NO) and prostacyclin (PGI 2) can be released by vascular agents to synergize their effects on vascular relaxation. In the present study we assess whether NO could affect PGI 2 production. We evaluated the effect of NO on PGI 2-mediated arachidonic acid (AA)-induced relaxation in the perfused heart. We used cultured endothelial cells to characterize the mechanism involved in the NO effect on PGI 2 synthesis. AA-induced PGI 2 synthesis was enhanced when NO synthesis was inhibited. NO inhibited AA-induced relaxation and PGI 2 release in the coronary circulation. S-Nitroso-acetyl- dl-penicillamine (SNAP) decreased PGI 2 production in cultured endothelial cells. The SNAP effect was blunted by the inhibitor of soluble guanylate cyclase (LY-83,583) and the blocker of cGMP-dependent protein kinases (H-9). Specific cyclooxygenase-1 (COX-1) immunoprecipitation was associated to co-precipitation of four proteins. COX-1 showed neither serine nor threonine phosphorylation. One of the proteins that co-precipitated with COX-1 presented increased serine phosphorylation in the presence of SNAP. This effect was inhibited by the H-9. We suggest that NO, through cGMP-dependent protein kinases, produces the phosphorylation of a 104-kDa protein that is associated with inhibition in the activity of the COX-1, decreasing PGI 2 synthesis and thereby decreasing coronary PGI 2-mediated vasodilatation.